title: [NF-κb inhibitor PDTC enhances tumor necrosis factor α-induced apoptosis of gastric cancer cell SGC-7901].
abstract: OBJECTIVE
  To investigate the effect of PDTC (inhibitor of NF-κb) on apoptosis of human gastric cancer cell line SGC-7901 induced by tumor necrosis factor α (TNF-α) and explore the related mechanisms.
  
  
  METHODS
  After the treatment with different concentrations of PDTC, TNF-α or PDTC combined with TNF-α on gastric cancer cell line SGC-7901, the growth inhibition of SGC-7901 was measured by MTT assay. Hoechst was used to assess SGC-7901 cell apoptosis. The protein expressions of survivin and caspase-3 were detected by Western blot assay.
  
  
  RESULTS
  The growth inhibition rate of SGC-7901 induced by PDTC (15, 30, 60, 100 μmol/L) was (12.14±0.91)%, (20.00±1.11)%, (37.63±1.01)% and (41.46±1.07)%. Different concentrations of PDTC all inhibited the growth of SGC-7901 significantly (all P<0.01), The growth inhibition rate of SGC-7901 induced by 25 mg/L TNF-α was (2.38±0.67)%, which could not significantly inhibit the growth of SGC-7901 [control (1.50±0.81)%], while TNF-α of 50, 100, 150 mg/L could inhibit the growth of SGC-7901 significantly [(4.53±0.85)%, (4.43±0.70)% and (4.74±1.07)%, all P<0.05]. PDTC (15 μmol/L) combined with TNF-α (25, 50, 100, 150 mg/L) significantly increased the cell growth inhibition rate compared with TNF-α alone or PDTC 15 μmol/L alone (all P<0.01). Hoechst assay showed that 100 mg/L TNF-α, 15 μmol/L PDTC and combination of above two all induced cell apoptosis (P<0.01), and the combination group had significantly higher percentage of cell apoptosis (P<0.01). Survivin protein was significantly down-regulated in combination group as compared with single TNF-α (100 mg/L) group, but was not significant down-regulated as compared with single PDTC (15 μmol/L) group. Caspase-3 protein expression was significantly increased in combination group as compared with other two groups.
  
  
  CONCLUSIONS
  PDTC can enhance the cell apoptosis induced by TNF-α, which may be associated with the blocking of TNF-α-activated NF-κB signaling pathway by PDTC, the down-regulation of survivin expression, and up-regulation of caspase-3 expression.
authors.affiliation: Department of General Surgery, Qingdao Municipal Hospital, Qingdao 266071, China. slliyang@163.com.
authors.forename: Ming-zheng
authors.initials: MZ
authors.lastname: Cao
authors.forename: Wei-zheng
authors.initials: WZ
authors.lastname: Mao
authors.forename: Gui-liang
authors.initials: GL
authors.lastname: Ma
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D000077022:Survivin; D013859:Thiocarbamates / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D000077022:Survivin; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C066229:prolinedithiocarbamate; D011392:Proline; C505407:CASP3 protein, human; D053148:Caspase 3